TAILIEUCHUNG - Chapter 005. Principles of Clinical Pharmacology

Drugs interact with specific target molecules to produce their beneficial and adverse effects. The chain of events between administration of a drug and production of these effects in the body can be divided into two components, both of which contribute to variability in drug actions. The first component comprises the processes that determine drug delivery to, and removal from, molecular targets. | Chapter 005. Principles of Clinical Pharmacology Drugs interact with specific target molecules to produce their beneficial and adverse effects. The chain of events between administration of a drug and production of these effects in the body can be divided into two components both of which contribute to variability in drug actions. The first component comprises the processes that determine drug delivery to and removal from molecular targets. The resultant description of the relationship between drug concentration and time is termed pharmacokinetics. The second component of variability in drug action comprises the processes that determine variability in drug actions despite equivalent drug delivery to effector drug sites. This description of the relationship between drug concentration and effect is termedpharmacodynamics. As discussed further below pharmacodynamic variability can arise as a result of variability in function of the target molecule itself or of variability in the broad biologic context in which the drug-target interaction occurs to achieve drug effects. Two important goals of the discipline of clinical pharmacology are 1 to provide a description of conditions under which drug actions vary among human subjects and 2 to determine mechanisms underlying this variability with the goal of improving therapy with available drugs as well as pointing to new drug mechanisms that may be effective in the treatment of human disease. The first steps in the discipline were empirical descriptions of the influence of disease X on drug action Y or of individuals or families with unusual sensitivities to adverse drug effects. These important descriptive findings are now being replaced by an understanding of the molecular mechanisms underlying variability in drug actions. Thus the effects of disease drug coadministration or familial factors in modulating drug action can now be reinterpreted as variability in expression or function of specific genes whose products determine

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